Brunel, T. | Search bioRxiv

bioRxiv2026

Engram and neural underpinning dynamics of the long-lasting childhood olfactory memory

Olfactory childhood memories are particularly important for forming ones identity. However, we dont know how they exert their privileged influence and shape brain structure. To address this, we modeled childhood olfactory memory in mice based on a human survey indicating that our earliest olfactory memory arises from repeated positive experiences paired with a pleasant odorant. Accordingly, mice were exposed during childhood to a pleasant odorant in a playful environment. In adulthood, memory recall relied on neonatal-born granule cells in the olfactory bulb, as their optogenetic silencing impaired retrieval, and on increased functional connectivity in the reward system. With age, memory persistence depended on re-exposure to the childhood odorant and was associated with the disengagement of neonatal-born granule cells, alongside with strengthened limbic functional connectivity. Together, these findings identify neonatal neurons as a key substrate for encoding childhood olfactory memory and reveal dynamic reorganization of brain networks supporting its long-term significance.

neuroscience↗

bioRxiv2025

Drug-induced versus non-pharmacological wakefulness: similar or different states? A whole brain analysis in TRAP2 transgenic mice

A large body of data indicate that the aminergic, cholinergic and hypocretin/orexin neurons are responsible for inducing wakefulness. However, recent data showed that other systems might also play a key role. Further, wakefulness induced by different drugs versus non-pharmacological means could be generated by different populations of neurons. To address these questions, we evaluated at the whole brain level in the same mice using TRAP2 model whether the same neurons were activated by the wake-inducing drugs modafinil and solriamfetol versus non-pharmacological wake. Our results show that several subcortical structures such as the bed nucleus of the stria terminalis, central amygdalar nucleus, paraventricular hypothalamic and thalamic and supraoptic nuclei, lateral parabrachial nucleus and lateral reticular area (including its noradrenergic neurons) are significantly more activated by solriamfetol than modafinil and non-pharmacological wakefulness. In contrast, a second category of structures including the orexin neurons, the parasubthalamic and laterodorsal tegmental nucleus are strongly activated in all types of induced wake. Further, some classical wake systems like the dopaminergic neurons of the ventral tegmental area or the dorsal raphe nucleus and the noradrenergic neurons of the locus coeruleus are either very poorly or not strongly activated. These results reveal that many structures not previously involved in wakefulness might play a key role in regulating the state and that some structures might be more recruited by solriamfetol than modafinil or non-pharmacological wakefulness. Our results are particularly relevant for pathologies such as hypersomnia. They open a new era in the study of the mechanisms responsible for inducing wakefulness.

neuroscience↗